S1P1 Contributes to Endotoxin-enhanced B-Cell Functions Involved in Hypersensitivity Pneumonitis.
Am J Respir Cell Mol Biol
; 63(2): 209-218, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32289229
ABSTRACT
In a proportion of patients with hypersensitivity pneumonitis, the biological and environmental factors that sustain inflammation are ill defined, resulting in no effective treatment option. Bioaerosols found in occupational settings are complex and often include Toll-like receptor ligands, such as endotoxins. How Toll-like receptor ligands contribute to the persistence of hypersensitivity pneumonitis, however, remains poorly understood. In a previous study, we found that an S1P1 (sphingosine-1-phosphate receptor 1) agonist prevented the reactivation of antigen-driven B-cell responses in the lung. Here, we assessed the impact of endotoxins on B-cell activation in preexisting hypersensitivity pneumonitis and the role of S1P1 in this phenomenon. The impact of endotoxins on pre-established hypersensitivity pneumonitis was studied in vivo. S1P1 levels were tracked on B cells in the course of the disease using S1P1-eGFP knockin mice, and the role of S1P1 on B-cell functions was assessed using pharmacological tools. S1P1 was found on B cells in experimental hypersensitivity pneumonitis. Endotoxin exposure enhanced neutrophil accumulation in the BAL of mice with experimental hypersensitivity pneumonitis. This was associated with enhanced CD69 cell-surface expression on lymphocytes in the BAL. In isolated B cells, endotoxins increased cell-surface levels of costimulatory molecules and CD69, which was prevented by an S1P1 agonist. S1P1 modulators also reduced TNF production by B cells and their capacity to trigger T-cell cooperation ex vivo. An S1P1 ligand directly inhibited endotoxin-induced B-cell activation.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Endotoxinas
/
Alveolitis Alérgica Extrínseca
/
Receptores de Esfingosina-1-Fosfato
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article